Glycolysis inhibition and its effect in doxorubicin resistance in neuroblastoma

Bean, J. F.; Qiu, Y. Y.; Yu, S.; Clark, S.; Chu, F.; Madonna, M. B.

J Pediatr Surg. 2014 Jun 4; 49(6):981-4

Abstract

BACKGROUND/PURPOSE: A common trait among cancers is the increased level of glycolysis despite adequate oxygen levels to support aerobic respiration. This has been shown repeatedly in different human malignancies. Glycolysis inhibitors, especially 3-bromopyruvate, have been shown to be effective chemotherapeutic agents. The effect of glycolysis inhibition upon chemotherapy resistance is relatively unknown. METHODS: Wild-type and doxorubicin-resistant lines of neuroblastoma (SK-N-SH and SK-N-Be(2)C) were used in this study. Using an MTT assay, the IC50 of 3-BrPA was determined. Subsequently, doxorubicin-resistant cell lines were treated with 3-bromopyruvate, doxorubicin, and 3-bromopyruvate with doxorubicin. Additionally, a luminescence ATP detection assay was used to measure intracellular ATP levels, and a lactate assay was used to determine intracellular lactate levels. All experiments were repeated in hypoxic conditions. RESULTS: Treatment with 3-bromopyruvate and doxorubicin significantly decreased the mean cell viabilities at 24, 48, and 72hours in normoxic conditions. A similar response was replicated in hypoxic conditions. Treatment with 3-bromopyruvate significantly decreased intracellular ATP and lactate levels. CONCLUSION: Glycolysis inhibitors such as 3-bromopyruvate could prove to become an effective means by which chemotherapy resistance can be overcome in human neuroblastoma.

Lurie Children's provides healthcare regardless race, color, religion (creed), sex, gender identity or expression, sexual orientation, national origin (ancestry), or disability. Financial assistance for medically necessary services is based on family income and hospital resources, and is provided to children under age 21 whose primary residence is in Illinois, Indiana, and Wisconsin.

Lurie Children's complies with applicable federal civil rights laws and does not discriminate on the basis of race, color, national origin, religion, sex, sexual orientation, gender identity or expression, age, or disability.